Activation of molecular oxygen and its use in stereoselective tetrahydrofuran-syntheses from δ,ε-unsaturated alcohols

Abstract

Bishomoallylic alcohols (pent-4-en-1-ols) underwent efficient oxidative cyclizations, if treated with O(2) and bis{2,2,2-trifluoromethyl-1-[(1R,4S)-1,7,7-trimethyl-2-(oxo-kappaO)bicyclo[2.2.1]hept-3-yliden]ethanolato-kappaO}cobalt(ii) in solutions of 2-propanol at 60 degrees C. Ring closures occurred diastereoselectively and afforded 2,3-trans- (96% de), 2,4-cis- (approximately 60% de), and 2,5-trans-substituted (>99% de) (phenyl)tetrahydrofur-2-ylmethanols as major components. Formation of bicyclic compounds and a 2,3,4,5-substituted oxolane was feasible as exemplified by syntheses of oxabicyclo[4.3.0]nonylmethanols and a derivative of natural product magnosalicin in 61-72% (90-99% de). The effectiveness of tetrahydrofuran synthesis was critically dependent on (i) solvent, (ii) reaction temperature, (iii) initial cobalt concentration, (iv) chain length between hydroxyl and vinyl groups, and (v) substitution at reacting entities. A sequence is proposed for rationalizing observed selectivities.

Concise Total Syntheses of Amphidinolides C and F

“…An oxidative Mukaiyama cyclization reaction opened a concise entry into the tetrahydrofuran sector G 53. 54 Our foray is distinguished by the fact that the chosen cyclization precursor 44 , which is readily available from the enantiopure epoxide 43 ,55 comprises two different π‐systems amenable to oxidation (Scheme ). Yet, the cobalt‐catalyzed reaction proved exquisitely chemoselective in that only the alkene site of 44 reacted while the alkyne remained untouched, thus furnishing the trans ‐disubstituted tetrahydrofuran 45 as the only detectable isomer in consistently high yield.…”

The direct oxidative diene cyclization and related reactions in natural product synthesis

“…Due to the close relation to type B cyclizations, they can be classified as type B’ (Scheme 3). Reagents that mediate this type of reaction are Re(VII), Cr(VI) and Co(II) complexes [26–29]. Again, the observed efficiency and stereoselectivity for this class of oxidative cyclization reactions is high.…”

“…In fact, in these cases, mostly a trans -selectivity for the cyclization event is observed, due to the loose coordination. The most prominent oxidants to promote such type C reactions are Co(II) and Re(VII) complexes [27–29]. Reactions where a 5- and/or 6-(di)hydroxy group directs an oxidizing reagent to an internal alkene to form an epoxide followed by a subsequent cyclization are not covered in this article as these are different in mechanism since the oxidation and cyclization are two distinct events and do not occur in the same step [3].…”

Functionalized Tetrahydrofurans from Alkenols and Olefins/Alkynes via Aerobic Oxidation−Radical Addition Cascades

“…To combine advantages of catalysis, stereoselective synthesis, and radical chemistry for synthesis of tetrahydrofuran-derived natural products, − we chose to functionalize the alkenol double bond in a sequence of polar and free radical reactions. ,, This sequence of transformation steps is not available from oxidation catalysis or radical chemistry alone. For our strategy, we selected oxidation catalysis to construct the tetrahydrofuran ring.…”